Submission Number: JIM-4-12-18

Abstract Number: 324

HIGHER-RESOLUTION MAPPING AND CHARACTERIZATION OF OVULATION RATE INDUCED AND AROMATASE ACTIVITY INDUCED QTL IN MICE.

Jimmy L Spearow, Marylynn Barkley, Charity L Turner, Oriole M Moeras, Nicholas J Alcaraz, Tuan Nguyen, Aruna Venkatesan, Diana Huang, Leslie Sullivan and Brita C Hugins

Section on Neurobiology Physiology and Behavior, University of California at Davis, Davis, CA ¹

Abstract:
The tremendous inter-individual variability in ovarian response to gonadotropins complicates ovulation and fertility induction programs in many vertebrate species. We continued to use reproductive congenic strains of mice to higher-resolution map and characterize Quantitative Trait Loci (QTL) controlling 6-fold genetic differences in Ovulation Rate Induced (ORI), and 20-fold differences in Aromatase Activity Induced (AAI) between A/J and C57BL/6J (B6) strain mice. Previous studies mapped and confirmed significant ORI QTL on mouse Chromosome (Chr) 2, 6 and X, as well as AAI QTL on Chr 2 and 4. We continued to higher-resolution map these QTL by progeny testing congenic strains which segregate only at narrow Chr regions flanking each QTL. Significant to highly significant QTL controlling AAI and/or ORI were mapped with increased resolution to regions of distal Chr 4 (Aaiq1), central Chr 2 (Aaiq2/Oriq2), proximal Chr 2 (Aaiq3/Oriq6), central Chr 6 (Oriq3) and Chr X (Oriq4). Each Aaiq1 and Aaiq2 allele doubled AAI (P<0.0001). Oriq2, Oriq3, Oriq4, and Oriq6 were all significant to highly significant on a genome wide basis with additive effects of 2.4 to 6.8 eggs per allele. Characterization of candidate genes revealed nucleic acid sequence polymorphisms in Cyp19 (P450 Aromatase) and other candidate genes. Preliminary data using luciferase reporter assays suggest strain differences in granulosa cell aromatase promoter activity. These QTL mapping and pharmacogenomic studies further characterize a class of genes (AAI/ORI QTL) which alter estrogen production, follicle maturation and ovulation rate. Identification of molecular genetic markers for reproductive QTL is essential for efficient selection for improved reproductive performance in livestock as well as for optimization of hormonal treatments for diverse hormone-response genotypes in a wide range of mammalian species. Support NSF 95-07872; NSF 99-86077. .

Keywords: Hormone Induced Ovulation Aromatase Genetics Mapping QTL Mice

This abstract is being presented at: 8:00 AM in session:
Gonadal Function